Diminished hypoxic ventilatory responses in near-miss sudden infant death syndrome

Abstract

The ventilatory response to hypoxia and to hypercarbia was assessed in 36 near-miss sudden infant death syndrome (N.M SIDS) and 23 control infants. Base-line measurements during non-REM sleep documented no significant difference in respiratory frequency, alveolar CO2 and O2 partial pressure (PAco2 and PAo2) or tidal volume between the N-M SIDS and control infants. In the N.M SIDS group, mean inspiratory flow and minute ventilation (VI) were significantly lower than in the control group (p less than 0.001 and p less than 0.01, respectively), and the slope of the ventilatory response to hypercarbia ((delta VI/Torr Paco2) was only 21 +/- 1.9 (SE) ml.kg-1 min-1 Torr PAco2 compared with 62 +/- 3.5 in controls (p less than 0.001). For both groups, the increase in ventilation with hypoxia appeared linear within the PAo2 range assessed (65-115 Torr) and was therefore expressed as the slope of the delta VI/PAo2 plot (ml.kg-1 min-1 per Torr PAo2). The slope of the hypoxic ventilatory response was significantly less in the N-M SIDS than in the control group, -8.3 +/- 1.0 VS. -19.9 +/- 1.5, respectively (p less than 0.001). In summary, in comparison to control infants, N-M SIDS infants as a group have a significantly smaller increase in VI in response to hypoxia as well as to hypercarbia.

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

“…Thus, the 5-HT system may be very important for responding to these exogenous stressors, so that a defect in this system could compromise a vulnerable individual. These observations may be relevant to sudden infant death syndrome, which has previously been linked to abnormalities in the 5-HT system (Paterson et al, 2006), and has been associated with defects in control of body temperature and breathing (Shannon et al, 1977;Hunt et al, 1981;Dunne and Matthews, 1988).…”

Sudden Infant Death Syndrome Is Not Associated with the Mutation of PHOX2B Gene, a Major Causative Gene of Congenital Central Hypoventilation Syndrome

“…Data are accumulating that specific genotypes link to impaired brainstem regulation of breathing or other autonomic control as a risk factor for SIDS. Several reports have described near-miss SIDS infants as having a defect in hypercarbic and hypoxic ventilatory arousal responses similar to CCHS patients (Hunt et al 1981;McCulloch et al 1982). The receptor tyrosine kinase RET (rearranged during transfection) proto-oncogene (RET) and the glial cell line-derived neurotrophic factor (GDNF) signaling pathways play significant roles in the development of the respiratory center.…”

“…In addition, rebreathing of expired hypercapnic gases has been hypothesized as one of the major pathophysiological mechanisms underlying the risk due to prone position. SIDS and near-miss SIDS infants are considered to have a defect in hypoxic and hypercapneic response similar to CCHS (Shannon et al 1977;Hunt et al 1981).…”

Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

“…It was reported that the patients who had a history of near-miss death from sudden infant death syndrome (Hunt et al 1981) and asthma attacks , or who experienced high altitude pulmonary edema had blunted hypoxic chemosensitivity. From these clinical studies, we speculated that persons with a blunted hypoxic ventilatory response may have a weak defense response to hypoxic episodes and be susceptible to fatal respiratory disturbances.…”

“…This hypoxic ventilatory response may be important in some respiratory diseases that can trigger life-threatening episodes. Hunt et al (1981) reported that infants with sudden infant death syndrome had lower hypoxic ventilatory responses than the control group. We found that persons with near fatal asthma showed lower hypoxic ventilatory responses than normal subjects and asthma patients without experience of near fatal asthmatic attack .…”